The most important objective in this proposal is to study the metabolism of N(G)-monomethyl-L-arginine, an endogenously synthesized compound, and to identify one of its metabolites as N-methylurea; a compound which can be nitrosated to give rise to l-N-methyl, l-N-nitrosourea, one of the most potent carcinogens known. This will be pursued with the following aims: (1) To study the metabolic pathway of N(G)-monomethyl-L-arginine, which arises from the in vivo proteolytic degradation of methylated proteins. The various initial possible metabolic reactions of N(G)-monomethyl-L-arginine involve hydrolytic cleavage of the compound with an arginase-type enzyme, oxidative demethylation, and decarboxylation of N(G)-mono- and N(G)-dimethyl-L-arginines. (2) To investigate the possible formation of N-methylurea from N(G)-monomethyl-L-arginine in vivo and in vitro, employing organ perfusion as well as whole rat. (3) To further purify protein methylase I which methylates the guanidino group of protein-bound arginine residues and thereby provides for free N(G)-monomethyl-L-arginine to form after intracellular proteolysis of the methylated proteins. (4) To investigate the possible anti-tumor effects of N(G)-monomethyl-L-arginine on tumor cells in tissue or cell culture. Thus, not only will the metabolic studies on N(G)-monomethyl-L-arginine yield important biochemical knowledge, but also the demonstration of endogenous formation of N-methylurea from N(G)-monomethyl-L-arginine will be the first proof that l-N-methyl, l-N-nitrosourea could indeed be formed in vivo.